Host−[2]Rotaxanes as Cellular Transport Agents

Abstract

Host-[2]rotaxanes, containing a diarginine-derivatized dibenzo-24-crown-8 (DB24C8) ether as the ring and a cyclophane pocket or an aromatic cleft as one blocking group, are cell transport agents. These hosts strongly associate with a variety of amino acids, dipeptides, and fluorophores in water (1 mM phosphate buffer, pH 7.0), DMSO, and a 75/25 (v/v) buffer to DMSO solution. All peptidic guests in all solvent systems have association constants (K(A)'s) in the range of 1 x 10(4) to 5 x 10(4) M(-)(1), whereas the K(A) range for the fluorophores is 1 x 10(4) to 9 x 10(5) M(-)(1). Association constants for the cyclophane itself, cyclophane 3, are smaller. These values are in the 1 x 10(3) to 5 x 10(3) M(-)(1) range, which shows that the rotaxane architecture is advantageous for guest binding. Cyclophane-[2]rotaxane 1 efficiently transports fluorescein and a fluorescein-protein kinase C (PKC) inhibitor into eukaryotic COS-7 cells, including the nucleus. Interestingly, cleft-[2]rotaxane 2 does not transport fluorescein as efficiently, even though the results from the fluorescence assays show that both [2]rotaxanes bind fluorescein with the same ability.

An Artificial Supramolecular Nanozyme Based on β-Cyclodextrin-Modified Gold Nanoparticles

“…Cyclodextrins are a series of cyclic saccharides possessing a hydrophobic inner cavity which enables the complexation of various organic, inorganic and biological molecules to form stable host-guest inclusion complexes [14,15] and supramolecular aggregates [16,17] in aqueous solution. Recently, the complexation of cyclodextrins and gold nanoparticles received special attention.…”

Controlled Submolecular Translational Motion in Synthesis: A Mechanically Interlocking Auxiliary

“…As well as being prototypical design elements for various types of molecular machines,1–5 rotaxanes (molecules in which one or more rings are held on one or more threads by bulky stoppers6) often dramatically change the properties of their components (including solubility,7 fluorescence,8 electroluminescence,9 and membrane transport10) and can protect encapsulated regions of threaded substrates from chemical attack11 and degradation 12. Interestingly, since they are molecular compounds—not supramolecular13 complexes (i.e., the atoms cannot be separated without breaking covalent bonds)—rotaxane architectures also, in principle, circumvent patents that only claim derivatives that branch out from a principal structure through continuous sequences of covalent bonds.…”

Recent Advances in the Synthesis of Ammonium-Based Rotaxanes

“…Structure-properties relationship has also been studied in regard to the binding ability [74]. These so-called host- [2]rotaxanes have been tested as cellular transport agent for fluorescein-PKC inhibitor conjugate [75][76][77][78].…”